Poly (ADP-ribose) polymerase inhibition improves endothelial dysfunction induced by hyperhomocysteinemia in rats.
BACKGROUND
We investigated the possible protective effect of poly (ADP-ribose) polymerase (PARP) inhibition in preventing endothelial dysfunction induced by hyperhomocysteinemia (Hhcy).


METHODS
Sprague-Dawley rats were divided into Hhcy group, Hhcy + 3-aminobenzamide(3-AB) group, control group and control + 3-AB group. A high-methionine diet was given to induce hyperhomocysteinemia. In Hhcy + 3-AB and control + 3-AB groups, rats were injected intraperitoneally with 3-AB (inhibitor of PARP). After 45 days, ultrastructural changes of aortas were observed by transmission electron microscope. Vascular reactivity of thoracic aortic rings was measured in organ chambers. PARP activity was detected. The levels of plasma total homocysteine, nitrite/nitrate, endothelin (ET)-1 and malondialdehyde were assayed.


RESULTS
Rats in Hhcy group developed severe hyperhomocysteinemia and significant loss of endothelial function as measured by both vascular rings and levels of nitrite/nitrate and ET-1. Malondialdehyde levels increased significantly in Hhcy rats compared with control rats. 3-AB improved Ach-induced, NO-mediated vascular relaxation and stabilized the level of nitrite/nitrate and ET-1. Obvious improvement of ultrastructure can be observed in Hhcy + 3-AB group.


CONCLUSIONS
These results suggest that pharmacological inhibition of PARP prevents the development of endothelial dysfunction in rats with hyperhomocysteinemia which may represent a novel approach to improve vascular dysfunction associated with hyperhomocysteinemia.
Yu
Xian
X
Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Cheng
Xiang
X
Xie
Jiang-jiao
JJ
Liao
Meng-yang
MY
Yao
Rui
R
Chen
Yong
Y
Ding
Ying-jun
YJ
Tang
Ting-ting
TT
Liao
Yu-hua
YH
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000473:pathology; D001549:Benzamides / Q000494:pharmacology*; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D020138:Hyperhomocysteinemia / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley
D001549:Benzamides; D019332:Endothelin-1; D004791:Enzyme Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D009569:Nitric Oxide; D008315:Malondialdehyde; C025160:3-aminobenzamide